Inhibition of HIV Type 1 Replication in CD4+ and CD14+ Cells Purified from HIV Type 1-Infected Individuals by the 2-5A Agonist Immunomodulator, 2-5AN6B

Two major interferon (IFN)-mediated antiviral defense enzymes are double-stranded (ds)RNA-dependent 2′,5′-oligoadenylate (2-5A) synthetase (2-5OAS) and p68 kinase (PKR). When activated by dsRNA, 2-5OAS synthesizes 2-5A, which binds to and activates RNase L. Activated RNase L hydrolyzes single-stranded viral RNA, thereby inhibiting viral protein synthesis. HIV-1 inhibits the IFN-mediated intracellular antiviral pathways. We have reported the synthesis and characterization of a nuclease-resistant 2-5A agonist (2-5AN6B) that overcomes the HIV-1 induced blockades by restoring the 2-5OAS/RNase L antiviral pathway (Homan JW, et al., J Acquir Immune Defic Syndr 2002;30:9–20). The objective of this study was to test the effect of 2-5AN6B on chronically infected CD4+ T lymphocytes and CD14+ monocytes derived from HIV-1-seropositive individuals. Wild-type HIV-1 replication was effectively inhibited by 2-5AN6B in CD4+ T lymphocytes and CD14+ monocytes purified from HIV-1 seropositive individuals (n = 18) compared to...